Head and Neck Squamous Cell Carcinoma (HNSCC) is a disease with significant morbidity and mortality, and without reliable indicators for prognosis, local recurrence, or presence of premalignant disease. This project is focused on validation of epigenetic, promoter methylation-based salivary rinse biomarkers that have been previously developed and published using a cohort of head and neck squamous cell carcinoma (HNSCC) patients and non-affected control subjects. Prior data shows these markers to be specific for head and neck cancer detection, and preliminary data show that detection of these markers in pretreatment salivary rinses in HNSCC patients is an independent prognostic indicator for local recurrence and poor survival. We will 1) define these markers in a separate validation cohort of salivary rinses from HNSCC patients to confirm association with local recurrence and poor overall survival. We will also 2) validate and test these markers in a clinical oral cancer detection cohort of malignant and premalignant lesions, respectively, previously collected under a U54 mechanism at the NYU College of Dentistry (U54DE014257, Dr. David Sirois). PUBLIC HEALTH RELEVANCE: This project is focused on validation of epigenetic, promoter methylation-based salivary rinse biomarkers that have been previously developed and published using a cohort of head and neck squamous cell carcinoma (HNSCC) patients and non-affected control subjects.